Abstract

Background - Several traditional cardiovascular risk factors, including hypertension, diabetes, and obesity have been associated with the risk of atrial fibrillation (AF). Literature on non-traditional risk predictors for AF is scarce, but high phosphorus, which has been linked with calcification and higher cardiovascular morbidity and mortality both in those with and without kidney dysfunction, may be one such marker. We assessed whether serum phosphorus levels were associated with AF incidence in a large community-based cohort in the US. Methods - Our analysis included 14,693 participants (25% African-American, 45% men) free of AF at baseline (1987-89), and with measurements of fasting serum phosphorus from the Atherosclerosis Risk in Communities (ARIC) study. Incidence of AF was ascertained through the end of 2008 from study visit ECGs, hospitalizations and death certificates. Cox proportional hazard models were used to estimate the hazards ratios (HR) of AF by serum phosphorous levels, adjusting for potential confounders. Results - During a median follow-up of 19.7 years, we identified 1659 incident AF cases. Higher serum phosphorus was associated with higher AF risk: multivariable HR: 1.20, 95% confidence interval (CI) 1.02-1.42 comparing extreme quintiles, p for trend=0.009 ( table ). The HR (95% CI) of AF with a 1 mg/dL increase in serum phosphorus was 1.15 (1.04-1.28). No significant interaction was seen by race (p=0.92) or gender (p=0.62). A possible interaction was seen between eGFR and phosphorus quintiles (p=0.05), with an increased risk of AF associated with higher serum phosphorus in those with eGFR =>90 mL/min/1.72m² but not among those with eGFR<90 ( table ). Conclusion - In this large population-based study, higher levels of serum phosphorus were associated with a higher incidence of AF. The association was seen only in those with normal kidney function. Table. Multivariable hazard ratio (95% confidence interval) of atrial fibrillation by quintiles of serum phosphorus levels, ARIC, 1987-2008 Serum Phosphorus Quintiles (mg/dL) P for trend ≤3.0 3.1-3.3 3.4-3.5 3.6-3.8 ≥3.9 Total population N (14,693) 3201 3287 2483 3048 2674 AF cases 380 373 260 360 286 Hazard Ratio (95% CI) * 1 (Ref.) 1.09 (0.94-1.26) 1.06 (0.90-1.25) 1.22 (1.05-1.42) 1.20 (1.02-1.42) 0.009 eGFR = > 90 mL/min/1.72m² N (10,149) 2143 2279 1723 2160 1844 AF cases 226 223 155 229 189 Hazard Ratio (95% CI) * 1 (Ref.) 1.06 (0.88-1.28) 1.01 (0.82-1.25) 1.26 (1.04-1.52) 1.37 (1.11-1.69) 0.001 eGFR <90 mL/min/1.72m² N (4544) 1058 1008 760 888 830 AF cases 154 150 105 131 97 Hazard Ratio (95% CI) * 1 (Ref.) 1.11 (0.88-1.39) 1.14 (0.88-1.39) 1.17 (0.91-1.49) 1.01 (0.77-1.32) 0.69 * Cox proportional hazard models adjusted for baseline age, gender, race, education, ARIC center, height, income, smoking status, drinking status, BMI, systolic blood pressure, diastolic blood pressure, antihypertensive medications, diabetes, serum calcium, estimated glomerular filtration rate (eGFR), prevalent stroke, prevalent heart failure and prevalent coronary heart disease Funding(This research has received full or partial funding support from the American Heart Association, National Center)

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